tbuckley/cabot-search huggingface dataset:
Case 15-2022: A 57-Year-Old Man with Persistent Cough and Pulmonary Opacities
Authors: Rachel S. Knipe, George A. Alba, Jeanna M. Harvey Barnes, Lida P. Hariri
Journal: New England Journal of Medicine (2022)

A 57-year-old man with polyarteritis nodosa was evaluated for cough and pulmonary opacities. Chest CT revealed multifocal clustered centrilobular nodules and opacities in a tree-in-bud pattern. A galactomannan test was positive. Diagnostic tests were performed.
Outcome of 177Lu-PSMA Radionuclide Treatment in Advanced Prostate Cancer and Its Association With Clinical Parameters
Authors: Duygu Has Simsek, Serkan Kuyumcu, Seyfullah Karadogan, Zeynep Gozde Ozkan, Emine Goknur Isik, Mert Basaran, Mehmet Oner Sanli, Yasemin Sanli
Journal: Clinical Nuclear Medicine (2022)

Purpose This study was set out to analyze the efficacy and safety of 177 Lu-PSMA-617 (LuPSMA) treatment in metastatic castration-resistant prostate cancer (mCRPC) patients. Patients and Methods Progressive mCRPC patients who received at least 1 cycle of LuPSMA therapy were evaluated retrospectively. Demographic, clinic, and histopathological data were documented. Treatment efficacy was determined based on biochemical response criteria (Prostate Cancer Clinical Trial Working Group 3), and toxicity rates were defined based on CTCAE v4.03. The prognostic significance of laboratory/clinical data and 68 Ga-PSMA PET/CT quantitative results were analyzed using SPSS Version 24.0. Results One hundred patients (median prostate-specific antigen [PSA] level, 75.7 ng/mL) who met the eligibility criteria were identified. The median number of cycles received per patient was 3 (range, 1–9). After the first cycles of LuPSMA, biochemical partial response, biochemical stable disease, and biochemical progressive disease were observed in 31%, 36%, and 33% of patients, respectively. Any PSA decline was determined in 60% of patients. After the fourth cycle of treatment, biochemical partial response, biochemical stable disease, and biochemical progressive disease were defined in 48%, 26%, and 26% of patients, respectively. The median overall survival (OS) from the first cycle of LuPSMA was 14 months. Patients who had any PSA response after the first cycle had significantly longer OS than nonresponders (median OS: 17 vs 9 months; P ≤ 0.001). Total PSMA-derived tumor volume ( P = 0.004), total PSMA activity per lesion ( P = 0.01), PSA ( P = 0.007), alkaline phosphatase ( P = 0.002), lactate dehydrogenase ( P &lt; 0.001), and hemoglobin ( P &lt; 0.001) were significant prognostic factors for OS in univariate Cox regression analysis. Conclusions LuPSMA therapy is a favorable treatment for mCRPC with remarkable therapeutic efficacy and low toxicity rates, even in progressive disease under standard therapies. Baseline PSMA-based tumor burden, PSA, alkaline phosphatase, lactate dehydrogenase, and hemoglobin were significant predictors of OS and can be useful for selection of the best candidate for LuPSMA therapy.
Single-cell deletion analyses show control of pro–T cell developmental speed and pathways by Tcf7, Spi1, Gata3, Bcl11a, Erg, and Bcl11b
Authors: Wen Zhou, Fan Gao, Maile Romero-Wolf, Suin Jo, Ellen V. Rothenberg
Journal: Science Immunology (2022)

As early T cell precursors transition from multipotentiality to T lineage commitment, they change expression of multiple transcription factors. It is unclear whether individual transcription factors directly control choices between T cell identity and some alternative fate or whether these factors mostly affect proliferation or survival during the normal commitment process. Here, we unraveled the impacts of deleting individual transcription factors at two stages in early T cell development, using synchronized in vitro differentiation systems, single-cell RNA-seq with batch indexing, and controlled gene-disruption strategies. First, using a customized method for single-cell CRISPR disruption, we defined how the early-acting transcription factors Bcl11a, Erg, Spi1 (PU.1), Gata3, and Tcf7 (TCF1) function before commitment. The results revealed a kinetic tug of war within individual cells between T cell factors Tcf7 and Gata3 and progenitor factors Spi1 and Bcl11a, with an unexpected guidance role for Erg. Second, we tested how activation of transcription factor Bcl11b during commitment altered ongoing cellular programs. In knockout cells where Bcl11b expression was prevented, the cells did not undergo developmental arrest, instead following an alternative path as T lineage commitment was blocked. A stepwise, time-dependent regulatory cascade began with immediate-early transcription factor activation and E protein inhibition, finally leading Bcl11b knockout cells toward exit from the T cell pathway. Last, gene regulatory networks of transcription factor cross-regulation were extracted from the single-cell transcriptome results, characterizing the specification network operating before T lineage commitment and revealing its links to both the Bcl11b knockout alternative network and the network consolidating T cell identity during commitment.
Mortality prediction of retinal vessel diameters and function in a long-term follow-up of haemodialysis patients
Authors: Roman Günthner, Lukas Streese, Susanne Angermann, Georg Lorenz, Matthias C Braunisch, Julia Matschkal, Renate Hausinger, David Stadler, Bernhard Haller, Uwe Heemann, Konstantin Kotliar, Henner Hanssen, Christoph Schmaderer
Journal: Cardiovascular Research (2022)

Retinal vessel diameters are candidate biomarkers of mortality prediction in large population-based studies. We aimed to investigate the predictive value of retinal vessel diameters and flicker-induced retinal arteriolar and venular dilation on all-cause mortality in long-term follow-up of haemodialysis patients.Retinal vessel diameters as well as maximum arteriolar (aMax) and venular dilation (vMax) were investigated in 275 and 214 haemodialysis patients, respectively. Patients were observed in a long-term follow-up for a median period of 73 months. About 36% (76/214) and 41% (113/275) of patients died. Arteriolar and venular diameters were 175 ± 19 and 208 ± 20 µm, respectively. Median aMax and vMax were 1.6 (0.3-3.3) and 3.2 (2.0-5.1)%. Patients within the lowest tertile of vMax showed lower 5-year survival rates compared with the highest tertile (50.6 vs. 82.1%) and also exhibited a higher incidence of infection-related deaths (21.7 vs. 4.0%). Univariate hazard ratio (HR) per standard deviation increase of vMax for all-cause mortality was 0.69 (0.54-0.88) and was even more pronounced for infection-related mortality [HR 0.53 (0.33-0.83)]. Regarding all-cause mortality, multivariate adjustment for eight non-retinal mortality predictors including interleukin-6 did not attenuate the HR relevantly [0.73 (0.54-0.98)]. Arteriolar and venular diameters did not predict all-cause nor cardiovascular and infection-related mortality.Long-term follow-up of patients on haemodialysis demonstrated the potential of retinal venular dilation capacity for mortality prediction, which was most pronounced for infection-related mortality. In the same cohort, retinal arteriolar and venular diameters showed no predictive value for hard endpoints. Retinal venular dilation but not arteriolar and venular diameters is a valuable diagnostic biomarker for risk prediction in patients with end-stage renal disease and should be considered for monitoring of critically ill patients.
Anti‐inflammatory effect of <scp>siRNAs</scp> targeted <i>il‐4</i> and <i>il‐13</i> in a mouse model of allergic rhinitis
Authors: Igor Shilovskiy, Alexandra Nikonova, Ekaterina Barvinskaia, Mariya Kaganova, Aleksandr Nikolskii, Lyudmila Vishnyakova, Valeriia Kovchina, Kirill Yumashev, Artem Korneev, Olga Petukhova, Dmitry Kudlay, Valeriy Smirnov, Sergey Andreev, Ksenia Kozhikhova, Artem Shatilov, Anastasiia Shatilova, Artem Maerle, Ilya Sergeev, Dmitry Trofimov, Musa Khaitov
Journal: Allergy (2022)

Appendix S1 Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Health outcomes in people 2 years after surviving hospitalisation with COVID-19: a longitudinal cohort study
Authors: Lixue Huang, Xia Li, Xiaoying Gu, Hui Zhang, LiLi Ren, Li Guo, Min Liu, Yimin Wang, Dan Cui, Yeming Wang, Xueyang Zhang, Lianhan Shang, Jingchuan Zhong, Xinming Wang, Jianwei Wang, Bin Cao
Journal: The Lancet Respiratory Medicine (2022)
Adenylate cyclase type 9 antagonizes cAMP accumulation and regulates endothelial signalling involved in atheroprotection
Authors: Yohann Rautureau, Marianne Berlatie, Daniel Rivas, Kurunradeth Uy, Alexandre Blanchette, Géraldine Miquel, Marie-Ève Higgins, Mélanie Mecteau, Audrey Nault, Louis Villeneuve, Véronique Lavoie, Gabriel Théberge-Julien, Geneviève Brand, Line Lapointe, Maxime Denis, Camille Rosa, Annik Fortier, Lucie Blondeau, Marie-Claude Guertin, Marie-Pierre Dubé, Éric Thorin, Jonathan Ledoux, David Rhainds, Éric Rhéaume, Jean-Claude Tardif
Journal: Cardiovascular Research (2022)

Abstract Aims The adenylate cyclase type 9 (ADCY9) gene appears to determine atherosclerotic outcomes in patients treated with dalcetrapib. In mice, we recently demonstrated that Adcy9 inactivation potentiates endothelial function and inhibits atherogenesis. The objective of this study was to characterize the contribution of ADCY9 to the regulation of endothelial signalling pathways involved in atherosclerosis. Methods and results We show that ADCY9 is expressed in the endothelium of mouse aorta and femoral arteries. We demonstrate that ADCY9 inactivation in cultured endothelial cells paradoxically increases cAMP accumulation in response to the adenylate cyclase activators forskolin and vasoactive intestinal peptide (VIP). Reciprocally, ADCY9 overexpression decreases cAMP production. Using mouse femoral artery arteriography, we show that Adcy9 inactivation potentiates VIP-induced endothelial-dependent vasodilation. Moreover, Adcy9 inactivation reduces mouse atheroma endothelial permeability in different vascular beds. ADCY9 overexpression reduces forskolin-induced phosphorylation of Ser157-vasodilator-stimulated phosphoprotein (VASP) and worsens thrombin-induced fall of RAP1 activity, both leading to increased endothelial permeability. ADCY9 inactivation in thrombin-stimulated human coronary artery endothelial cells results in cAMP accumulation, increases p-Ser157-VASP, and inhibits endothelial permeability. MLC2 phosphorylation and actin stress fibre increases in response to thrombin were reduced by ADCY9 inactivation, suggesting actin cytoskeleton regulation. Finally, using the Miles assay, we demonstrate that Adcy9 regulates thrombin-induced endothelial permeability in vivo in normal and atherosclerotic animals. Conclusion Adcy9 is expressed in endothelial cells and regulates local cAMP and endothelial functions including permeability relevant to atherogenesis.
Mature neutrophils and a NF-κB-to-IFN transition determine the unifying disease recovery dynamics in COVID-19
Authors: Amit Frishberg, Emma Kooistra, Melanie Nuesch-Germano, Tal Pecht, Neta Milman, Nico Reusch, Stefanie Warnat-Herresthal, Niklas Bruse, Kristian Händler, Heidi Theis, Michael Kraut, Esther van Rijssen, Bram van Cranenbroek, Hans JPM. Koenen, Hidde Heesakkers, Mark van den Boogaard, Marieke Zegers, Peter Pickkers, Matthias Becker, Anna C. Aschenbrenner, Thomas Ulas, Fabian J. Theis, Shai S. Shen-Orr, Joachim L. Schultze, Matthijs Kox
Journal: Cell Reports Medicine (2022)

Disease recovery dynamics are often difficult to assess, as patients display heterogeneous recovery courses. To model recovery dynamics, exemplified by severe COVID-19, we apply a computational scheme on longitudinally sampled blood transcriptomes, generating recovery states, which we then link to cellular and molecular mechanisms, presenting a framework for studying the kinetics of recovery compared with non-recovery over time and long-term effects of the disease. Specifically, a decrease in mature neutrophils is the strongest cellular effect during recovery, with direct implications on disease outcome. Furthermore, we present strong indications for global regulatory changes in gene programs, decoupled from cell compositional changes, including an early rise in T cell activation and differentiation, resulting in immune rebalancing between interferon and NF-κB activity and restoration of cell homeostasis. Overall, we present a clinically relevant computational framework for modeling disease recovery, paving the way for future studies of the recovery dynamics in other diseases and tissues.
Stimulant Prescription Medications Among Persons Receiving Buprenorphine for Opioid Use Disorder With Prior Drug-Related Poisoning—Evidence of Net-Sum Gain
Authors: Judith I. Tsui
Journal: JAMA Network Open (2022)

Carrie M. Mintz, MD; Kevin Y. Xu, MD, MPH; Ned J. Presnall, MSW; Sarah M. Hartz, MD, PhD; Frances R. Levin, MD; Jeffrey F. Scherrer, PhD; Laura J. Bierut, MD; Richard A. Grucza, PhD
Clinical sequelae among individuals with pauci-symptomatic or asymptomatic Ebola virus infection and unrecognised Ebola virus disease in Liberia: a longitudinal cohort study
Authors: J Daniel Kelly, Collin Van Ryn, Moses Badio, Tamba Fayiah, Kumblytee Johnson, Dehkontee Gayedyu-Dennis, Sheri D Weiser, Travis C Porco, Jeffery N Martin, Michael C Sneller, George W Rutherford, Cavan Reilly, Mosoka P Fallah, J Soka Moses
Journal: The Lancet Infectious Diseases (2022)

Whether or not individuals with pauci-symptomatic or asymptomatic Ebola virus infection and unrecognised Ebola virus disease develop clinical sequelae is unknown. We assessed current symptoms and physical examination findings among individuals with pauci-symptomatic or asymptomatic infection and unrecognised Ebola virus disease compared with Ebola virus disease survivors and uninfected contacts.
Crystallographic landscape of SHP2 provides molecular insights for SHP2 targeted drug discovery
Authors: Yihui Song, Xinyu Yang, Shu Wang, Min Zhao, Bin Yu
Journal: Medicinal Research Reviews (2022)

Abstract The protein tyrosine phosphatase SHP2 encoded by PTPN11 is a promising therapeutic target for cancer therapy. The dynamic change of SHP2 between closed and open conformations under either physiological or pathological conditions provides opportunities to design SHP2 inhibitors for treating SHP2‐related diseases. To date, several SHP2 allosteric inhibitors have advanced into clinical trials as mono‐ or combined therapy of cancers. In this review, we provide an overview on the structural landscape of SHP2 under physiological and pathological conditions and also comprehensively analyze the binding models of SHP2/inhibitor complexes. Structural features of SHP2 under pathological conditions and co‐crystal structures of SHP2/inhibitor complexes will definitely facilitate structure‐guided design of SHP2 inhibitors. Finally, proteolysis targeting chimeric (PROTAC) based SHP2 degraders have shown therapeutic promise for cancer therapy and are also briefly discussed. We hope this review could provide crystallographic landscape for SHP2 targeted drug discovery.
Parallel Evolution of Ameloblastic <i>scpp</i> Genes in Bony and Cartilaginous Vertebrates
Authors: Nicolas Leurs, Camille Martinand-Mari, Sylvain Marcellini, Mélanie Debiais-Thibaud
Journal: Molecular Biology and Evolution (2022)

Abstract In bony vertebrates, skeletal mineralization relies on the secretory calcium-binding phosphoproteins (Scpp) family whose members are acidic extracellular proteins posttranslationally regulated by the Fam20°C kinase. As scpp genes are absent from the elephant shark genome, they are currently thought to be specific to bony fishes (osteichthyans). Here, we report a scpp gene present in elasmobranchs (sharks and rays) that evolved from local tandem duplication of sparc-L 5′ exons and show that both genes experienced recent gene conversion in sharks. The elasmobranch scpp is remarkably similar to the osteichthyan scpp members as they share syntenic and gene structure features, code for a conserved signal peptide, tyrosine-rich and aspartate/glutamate-rich regions, and harbor putative Fam20°C phosphorylation sites. In addition, the catshark scpp is coexpressed with sparc-L and fam20°C in tooth and scale ameloblasts, similarly to some osteichthyan scpp genes. Despite these strong similarities, molecular clock and phylogenetic data demonstrate that the elasmobranch scpp gene originated independently from the osteichthyan scpp gene family. Our study reveals convergent events at the sparc-L locus in the two sister clades of jawed vertebrates, leading to parallel diversification of the skeletal biomineralization toolkit. The molecular evolution of sparc-L and its coexpression with fam20°C in catshark ameloblasts provides a unifying genetic basis that suggests that all convergent scpp duplicates inherited similar features from their sparc-L precursor. This conclusion supports a single origin for the hypermineralized outer odontode layer as produced by an ancestral developmental process performed by Sparc-L, implying the homology of the enamel and enameloid tissues in all vertebrates.
A short prokaryotic Argonaute activates membrane effector to confer antiviral defense
Authors: Zhifeng Zeng, Yu Chen, Rafael Pinilla-Redondo, Shiraz A. Shah, Fen Zhao, Chen Wang, Zeyu Hu, Chang Wu, Changyi Zhang, Rachel J. Whitaker, Qunxin She, Wenyuan Han
Journal: Cell Host & Microbe (2022)
Comprehending the allergen repertoire of shrimp for precision molecular diagnosis of shrimp allergy
Authors: Christine Y. Y. Wai, Nicki Y. H. Leung, Agnes S. Y. Leung, Sai Ming Ngai, Punchama Pacharn, Yat Sun Yau, Jaime Sou Da Rosa Duque, Mike Y. W. Kwan, Orathai Jirapongsananuruk, Wai Hung Chan, Gilbert T. Chua, Qun Ui Lee, Surapon Piboonpocanun, Po Ki Ho, Joshua S. C. Wong, Shanshan Li, Kary J. Y. Xu, Gary W. K. Wong, Ka Hou Chu, Patrick S. C. Leung, Pakit Vichyanond, Ting Fan Leung
Journal: Allergy (2022)

Clinical management of shrimp allergy is hampered by the lack of accurate tests. Molecular diagnosis has been shown to more accurately reflect the clinical reactivity but the full spectrum of shrimp allergens and their clinical relevance are yet to be established. We therefore sought to comprehend the allergen repertoire of shrimp, investigate and compare the sensitization pattern and diagnostic value of the allergens in allergic subjects of two distinct populations.Sera were collected from 85 subjects with challenge-proven or doctor-diagnosed shrimp allergy in Hong Kong and Thailand. The IgE-binding proteins of Penaeus monodon were probed by Western blotting and identified by mass spectrometry. Recombinant shrimp allergens were synthesized and analyzed for IgE sensitization by ELISA.Ten IgE-binding proteins were identified, and a comprehensive panel of 11 recombinant shrimp allergens was generated. The major shrimp allergens among Hong Kong subjects were troponin C (Pen m 6) and glycogen phosphorylase (Pen m 14, 47.1%), tropomyosin (Pen m 1, 41.2%) and sarcoplasmic-calcium binding protein (Pen m 4, 35.3%), while those among Thai subjects were Pen m 1 (68.8%), Pen m 6 (50.0%) and fatty acid-binding protein (Pen m 13, 37.5%). Component-based tests yielded significantly higher area under curve values (0.77-0.96) than shrimp extract-IgE test (0.70-0.75). Yet the best component test differed between populations; Pen m 1-IgE test added diagnostic value only in the Thai cohort, whereas sensitizations to other components were better predictors of shrimp allergy in Hong Kong patients.Pen m 14 was identified as a novel shrimp allergen predictive of challenge outcome. Molecular diagnosis better predicts shrimp allergy than conventional tests, but the relevant component is population dependent.
Hepatology highlights
Authors: Roberto Alva‐Ruiz, Tiffany Wu, Francisco Idalsoaga, Resham Ramkissoon, Juan Pablo Arab, Sumera I. Ilyas
Journal: Hepatology (2022)

Alva‐Ruiz, Roberto; Wu, Tiffany; Idalsoaga, Francisco; Ramkissoon, Resham; Arab, Juan Pablo; Ilyas, Sumera I. Author Information
Should patients own their health records?
Authors: Angela Coulter
Journal: BMJ (2022)

Thank you for your interest in spreading the word about The BMJ.NOTE: We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. We do not capture any email address. Username * Your Email * Send To * You are going to email the following Should patients own their health records? Your Personal Message CAPTCHA This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
The paradox of artificial intelligence diversification in endoscopy: creating blind spots by exposing them
Authors: Fons van der Sommen
Journal: Endoscopy (2022)

Rarely have technological innovations had such broad impact across different scientific disciplines as the recent progress in artificial intelligence (AI) technology, which has enabled breakthroughs from cosmology [1] to protein folding [2]. In the field of gastrointestinal (GI) endoscopy, AI has also already made a lasting impression, with impressive results having been reported for a variety of applications [3] [4] [5]. While the pace of this development is remarkable, its focus has been rather narrow, as most studies have been concentrated around disease detection and/or staging. Only recently have the broader applications of AI within GI endoscopy started to be seriously explored.
When I use a word . . . . Some words about the climate
Authors: Jeffrey K Aronson
Journal: BMJ (2022)

In October 2021 the <i>Oxford English Dictionary</i> incorporated 61 new terms, almost all of them dealing with aspects of ecology, and specifically climate change. The list included many compound terms, several including the word climate itself, such as climate action, climate catastrophe, climate crisis, climate denial/denialism/denier, climate emergency, climate justice, climate refugee, climate sceptic, and climate strike. Others dealt with capture and storage of carbon, ecological sustainability, and the availability of food or water. This influx of new terms into the dictionary to some extent mirrors the world's preoccupation with greenhouse gas emissions. The UK contributes about 1% of global greenhouse gas emissions, of which about 76% is in carbon emissions, the rest coming from methane (16%), nitrous oxide (6%), and fluorinated gases (2%). The UK's greenhouse gas emissions fell by 9.5% in 2020 compared with 2019; carbon emissions fell by 6% (from 1.01% of the global burden to 0.95%), a larger percentage fall than in most other countries in the world.
Molecular detection of isoniazid monoresistance improves tuberculosis treatment: A retrospective cohort in France
Authors: Marwa Bachir, Lorenzo Guglielmetti, Simone Tunesi, Typhaine Billard-Pomares, Sheila Chiesi, Jérémy Jaffré, Hugo Langris, Valérie Pourcher, Frédéric Schramm, Nadine Lemaître, Jérôme Robert
Journal: Journal of Infection (2022)